Interrogation of G-quadruplex-protein interactions.

The ability to accurately examine the interaction of G-quadruplex DNA with proteins is essential for revealing the biological roles of these unusual DNA structures. In this regard, there are four primary G-quadruplex-related activities of proteins that have been studied including simple equilibrium binding, promotion or catalysis of G-quadruplex formation, dissociation of G-quadruplex structures, and covalent modification of G-quadruplexes, which includes both nucleolytic cleavage and nucleotide addition. Here, assays used to examine the interactions of G-quadruplexes with proteins will be reviewed and specific methods to study the interactions of G-quadruplexes from telomeric DNA sequences with a variety of proteins will be described. Importantly, this review emphasizes the importance of evaluating the integrity of the G-quadruplex being studied as single sequences can often form a variety of folded structures.